Healthy Male
Conditions
Keywords
Phase I, Safety, tolerability, healthy, major depressive disorder, thorough QT, maximum tolerated dose, elimination, heart electrical signal
Brief summary
This is a two part study. Part A will determine the maximum tolerated dose of TC-5214 administered to healthy male subjects in single ascending oral doses. This part of the study will define the highest dose of TC-5214 to be administered in Part B. Part B of this study will investigate the effect of TC-5214 on the electrical activity of the heart following single oral administration. The study will be carried out healthy male subjects in a four period crossover study with TC-5214 compared to placebo and oral moxifloxacin as a positive control. The safety, tolerability and pharmacokinetics of TC-5214 will also be evaluated.
Interventions
DRUGTC-5214
Single dose, oral tablets
OTHERPlacebo comparator
Single dose, oral tablets
DRUGMoxifloxacin
Single dose, oral encapsulated tablet
OTHERMoxifloxacin placebo comparator
Single dose, oral encapsulated tablet
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male 18 to 50 years old inclusive with suitable veins for cannulation or repeated venipuncture * Have a body mass index (BMI) between 19 and 30 kg/m2 inclusive and weigh at least 50 kg * Male subjects should be willing to use a double barrier method of contraception (condom with spermicide) from the first dose of investigational product until 3 months after the last dose of investigational product * Be able to understand and comply with the requirements of the study as judged by the investigator
Exclusion criteria
* History of any clinically significant medical, neurologic or psychiatric disease or disorder which, in the opinion of the Investigator and Sponsor may either put the subject at risk because of participation in the study, or influence the results of the subject's ability to participate in the study * History or presence of gastrointestinal (including irritable bowel disease), hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of study drug. Subjects with a history of surgery on the gastrointestinal tract (not including appendectomy or cholecystectomy) should also be excluded * History of seizure activity, including febrile seizures * Prolonged QTcF \>450 ms or shortened QTcF \<340 ms, or family history of Long QT Syndrome * Use of concomitant medications that prolong QT/QTc interval
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: The number of participants with adverse events | Up to 24 hours |
| Part B: The maximum mean change in time-matched ECG interval, measured from the onset of the QRS complex to the T point, using the best heart rate correction method (QTc). | Up to 24 hours |
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in laboratory assessments. | Up to 24 hours |
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in vital signs. | Up to 24 hours |
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in electrocardiogram (ECG). | Up to 24 hours |
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in physical examination. | Up to 24 hours |
Secondary
| Measure | Time frame |
|---|---|
| Part B: A change in the maximum of the mean change in time-matched ECG interval, measured from the onset of the QRS complex | Up to 24 Hours |
| Part B: Assay sensitivity by measuring the effect of moxifloxacin 400 mg on QTc compared to placebo | Up to 24 hours |
| Part A: TC-5214 Plasma and urine pharmacokinetic variable to be measured: including, C max, time to C max, Area Under Curve (AUC) (0-t), terminal half life, cumulative amount of drug excreted unchanged into urine from zero to time and renal clearance | Up to 72 Hours |
Countries
United Kingdom
Outcome results
None listed